Meta-Analysis of Parkinson's Disease Transcriptome Data Using TRAM Software: Whole Substantia Nigra Tissue and Single Dopamine Neuron Differential Gene Expression.

Elisa Mariani,Fabrizio Pizzetti,Andrea Tarozzi,Flavia Frabetti,Raffaella Casadei,Maria Chiara Pelleri,Ornit Chiba-Falek

doi:10.1371/journal.pone.0161567

Abstract

The understanding of the genetic basis of the Parkinson's disease (PD) and the correlation between genotype and phenotype has revolutionized our knowledge about the pathogenetic mechanisms of neurodegeneration, opening up exciting new therapeutic and neuroprotective perspectives. Genomic knowledge of PD is still in its early stages and can provide a good start for studies of the molecular mechanisms that underlie the gene expression variations and the epigenetic mechanisms that may contribute to the complex and characteristic phenotype of PD. In this study we used the software TRAM (Transcriptome Mapper) to analyse publicly available microarray data of a total of 151 PD patients and 130 healthy controls substantia nigra (SN) samples, to identify chromosomal segments and gene loci differential expression. In particular, we separately analyzed PD patients and controls data from post-mortem snap-frozen SN whole tissue and from laser microdissected midbrain dopamine (DA) neurons, to better characterize the specific DA neuronal expression profile associated with the late-stage Parkinson's condition. The default "Map" mode analysis resulted in 10 significantly over/under-expressed segments, mapping on 8 different chromosomes for SN whole tissue and in 4 segments mapping on 4 different chromosomes for DA neurons. In conclusion, TRAM software allowed us to confirm the deregulation of some genomic regions and loci involved in key molecular pathways related to neurodegeneration, as well as to provide new insights about genes and non-coding RNA transcripts not yet associated with the disease.

Highlights

Parkinson's disease (PD) is a common neurodegenerative disorders, the second after Alzheimer's disease (AD), with an estimated incidence of 1–2% in individuals over 60 years of age [1]
We filtered our analysis with criteria "substantia nigra" as specific area of interest and inclusion-exclusion restrictions, achieving a total of 11 series
According to RNA source, 9 series were included in the TRAM substantia nigra (SN) ONLY analysis and 3 series were included in the TRAM DA ONLY analysis (Fig 1 and Table 1)

Summary

Introduction

Parkinson's disease (PD) is a common neurodegenerative disorders, the second after Alzheimer's disease (AD), with an estimated incidence of 1–2% in individuals over 60 years of age [1]. It has been widely demonstrated that the degeneration of the dopamine (DA)-synthesizing cells of the substantia nigra (SN) pars compacta cause the common motor and non-motor symptoms of PD [2]. The development of PD usually leads to death in 10 years after diagnosis [4]. Even if novel therapeutic approaches are being investigated in order to slow or halt neuronal degeneration [5], the most efficient treatment of PD still remains the use of levodopa, to relieve PD motor symptoms by replacing the deficient neurotransmitter DA. The pathology of the disease is very complex and its etiology remains unknown, research has highlighted the pathological role of different factors, in addition to genetic predispositions

Methods

Results

Conclusion